Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 90, Issue 6, Pages 1191-1197Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.1110608
Keywords
ATRA; MDSCs; monocytes; nitric oxide; parasites; suppression
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Funding
- Brazilian National Research Council (CNPq)
- Rio de Janeiro State Science Foundation [Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)]
- National Institutes of Science and Technology (INCT-INPeTAm/CNPq/MCT)
- CNPq
- Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES
- Brazilian Ministry of Education)
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Th1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO-producing MDSCs could help immunity to L. major infection. Gr1(hi)(Ly6C(hi)) CD11b(hi) MDSCs elicited by L. major infection suppressed polyclonal and antigen-specific T cell proliferation. Moreover, L. major-induced MDSCs killed intracellular parasites in a NO-dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate into macrophages, increased development of lesions, parasite load, and T cell proliferation in draining LNs. Altogether, these results indicate that NO-producing MDSCs help protective immunity to L. major infection, despite suppressed T cell proliferation. J. Leukoc. Biol. 90: 1191-1197; 2011.
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